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Spanish search result creates vaccine that induces viral control without antiretroviral therapy in a significant percentage of subjects

checking vaccine 25A vaccine known as "HIV Vaccine Conserv" for the first time, produced significant response in prolonged viral control in a large minority of recipients, since they were taken out of antiretroviral therapy (ART). To date, a participant was out of antiretroviral therapy for seven months without having to resume. Introducing theConference on Retroviruses and Opportunistic Infections (CROI 2017)Beatriz Mothe said that viral control in subjects of this vaccine, occurred more frequently than spontaneous control of HIV observed in previous studies of treatment interruption.

Though a number of vaccine studies in monkeys have produced long-term viral suppression, this is the first human study that produced that effect.

Conserv HIV vaccines and study BCN01 

The study of BCN02 vaccine is still ongoing and is following single-dose study, BCN01, the researcher Beatriz Mothe reported last year (see reference).

The first study enrolled 15 people who started treatment immediately after HIV infection and has given them a single dose of a vaccine against HIV Conserv (aka "HIVconsv ').

For a more complete explanation than HIV Conserv vaccines are and how they workSee the report (in English and in another tab).In brief explanation, they contain selected antigens (immune-stimulating protein sequences or genes) of HIV that are highly conserved, hence the name. "Highly conserved" means that they are parts of the HIV virus can change less frequently, and that vary little in many variants of HIV.

The vaccine is therefore sections proteins from different HIV strains "aggregates" that generate a strong immune response to HIV, the virus which finds it difficult to "escape". HIV can not "afford to generate mutations that bypass the immune responses of the body because for that it would weaken ".

What this means is that the vaccine "pushes" the cellular mechanism of anti-HIV cells cells "T CD8" a response in order to become more powerful with less waste because the body does not generate responses which the virus you can easily escape. In BCN01 study by researchers it was established that this was exactly what had happened.

linfocito-depositphotos_49757357_original_vectBlood cell Lymphocyte

Study BCN02

For the second study, researchers worked with the same cast with 15 participants, giving them two more doses of the vaccine "HIV Conserv"Weeks 0 and 9. In addition, in the weeks 3, 4 and 5 three infusions were applied the "latency Inverter" Romidepsin, which is a stimulant drug of the immune system, which has been appliedin healing studies called "kick and kill 'cure HIV infection experiments of cure.

The idea of ​​using a vaccine against HIV, combined with Romidepsin is to use Romidepsin to stimulate viral production bursts (the awakening of viral reservoirs) while the viral participant is still under antiretroviral therapy (HAART). The immune response stimulated by the vaccine "see" these viral replication gusts, strengthening themselves and thus to fine-tune this response.

The HIV DNA in cells was measured at week 0, 3 weeks in the 5 while Romidepsin was being given, and the week 9. The proportion of CD8 cells that were sensitive to HIV effectively destructively was measured in weeks 0, 1, 3, 9, 10 and 13. Antiretroviral therapy was stopped in 17ª week on a break monitored pause antiretrovirals. Antiretroviral therapy was resumed in the subjects in which there was viral rebound.

Results

There were men and 14 1 woman in the study. The average age was 40 years and all had started HAART early - an average of three months and a maximum of 5 months after the estimated date of HIV infection. All had been on HAART for over three-four years. All of them were under regimens containing integrase inhibitor and its average score of CD4 was 728 cells / mm3 (minimum 416).

The vaccine produced led to symptoms like the flu and the most common side effects were headache, fatigue and muscle aches.

The three infusions of Romidepsin were accompanied by short bursts of viral production, despite HAART, in order to 50 400 copies / ml, with some viral blipes of 1000 copies / ml in all except one participant. These were accompanied by similar T cell production waves: CD4 counts rose about 200 cells / mm3 during each infusion, but were back to the level observed previously after three days. Note Translator .: Out of curiosity "look know more about this" romidesepin "and found something on wikipedia, in English and is as follows:

The romidepsina, also known as Istodax is an anticancer agent used in cutaneous T-cell lymphoma (CTCL) and other peripheral T cell lymphomas (PTCLs). Romidepsin is a natural product obtained from the bacterium Chromobacterium violaceum, and works by blocking enzymes known as histone deacetylases, thereby inducing apoptosis. [1] It is sometimes referred to as depsipeptide after the class of molecules to which it belongs. Romidepsin is marked and owned by Gloucester Pharmaceuticals, now a part of Celgene. [2]

Adverse effects The use of romidepsina is uniformly associated with adverse effects. [13] In clinical trials, the most common were nausea and vomiting, fatigue, infection, loss of appetite and blood disorders (including anemia, thrombocytopenia, and leukopenia). It has also been associated with infections and metabolic disorders (such as abnormal levels of electrolytes), skin reactions, changes in taste perception and changes in cardiac electrical conduction. [13]

This is an overview of something that I considered important to put here. Who want to know more just click Romidesepin- Opens in another tab, is in English but the Tgoogle radutor help excellent way

White Keyboard with Vaccination Button.

Although these viral production peaks, the amount of viral DNA in reservoir cells has not changed: a hope provided the original concept of "kick and kill" was that viral production bursts would be a "storm" of infected cells, but it does not seem to happen.

The anti-HIV responses CD8 cells increased during the study, both after the first vaccine dose and after the introduction of Romidepsin. But equally important, the type of immune response has to be characterized by a comprehensive response to all the HIV proteins to a situation where three quarters of the immune response was very aggressive to the highly conserved areas targeted by the vaccine.

Shutting down the viral control by ART

So far thirteen of the fifteen participants of the study remains interrupted their antiretroviral therapy. For the 8 13, viral load quickly jumped to the levels prior to HAART (average of about 100.000 copies / ml) within four weeks and they started again

Antiretroviral Therapy
It's not always like that. There are schemes with three tablets a day, once a day. As an example the combination of lamivudine in one tablet, associated with atazanavir, a capsule and Norvir, a tablet relativaemete small once daily.

.

However, for the other five participants, viral load just jumped intermittently to low levels (below 2000 copies / ml). So far, these five participants have remained out of their HAART after 6, 12, 19, 20 and 28 weeks, respectively. None have kept completely undetectable levels of viral load during this time; Instead what has been seen is a standard "blipes" mainly 200 copies / ml or so, but there was a case 2000 copies / ml before becoming undetectable again. A participant (in 19ª week without ART) had a slightly different pattern; initially he kept suppressed their viral load suddenly jumped to 2000 copies / ml in the seventh week, however, from the twelfth week, began to decline and is now below 200 copies / ml.

These five participants represent 38% of the group is considerably higher than 2% of people who usually control their viral load after stopping with ART.

What made the difference between being a "bounder" (borderline) and a "controller"?

The proviral DNA in cells mattered: the drivers were all within the lower half of viral load measurements checks. There was no correlation with the intensity of the immune response, but there was a correlation with its specificity: all drivers have a greater proportion of their immune responses attuned to the highly conserved regions of HIV.

Conclusions

It seems that if the vaccine has contributed to strengthening a phenomenon sometimes seen in people who very soon start treatment after infection. Such people naturally develop smaller RNA reservoirs and therefore retain some degree of more effective immune control of HIV because they lack the proliferation of virus strains that occurs in untreated people chronically. This proliferation overloads the ability of your immune system to adapt to it. The vaccine not only enhances this answer, but also redirects the most efficient immune response.

"This study is interesting because it is the first to demonstrate the post-treatment control - that is, by definition, the following:

The virus is present, but there is no viral rebound after stopping antiretroviral therapy, "said Sharon Lewin, Director of the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Australia. "But we also have to be careful - there was no control group and did not know that part of the intervention was important - The start of the vaccine? The second vaccine? Romidepsin? All of the above?

"At the same time so far in all other studies involving discontinuation of treatment and post-treatment control it was rare and most happens occasionally. This is a promising step and significant ahead. No doubt we need a follow-up study that is larger and have a control group that did not receive any intervention and a less complicated vaccine schedule. We would like to understand why some people control the infection in non-hazardous levels too - and to tell the truth, at this point we do not know the answer to that. "

Translated by Claudio Souza of Contents at the address belowSpanish control viral vaccine induces off ART in Nearly 40% of recipients Originally published by Gus Cairns in February 17 2017 to AIDSMAP.com

Reviewed by Mara Macedo

References

Mothe B et al.Viral control induced by vaccines HIVconsv & Romidepsin in early treated Individuals. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 119LB, 2017.

View the abstract on the conference website.

View the webcast of this presentation on the conference website.

See also Mothe B et al.Shaping CTL Immunodominance With Conserved HIV Vaccines After Early Treatment (BCN01).CROI 2016, Boston, abstract in 320, 2016.

View the abstract on the conference website

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